EXECUTIVE SUMMARY 4th Clinical Quality Signals, RCA and CAPAinfo.exlevents.com/rs/exlevents/images/C405-Executive... · 2014-10-20 · 3 INTRODUCTION: THE 4TH CLINICAL QUALITY SIGNALS,

Identifying Clinical Non-compliance, Conducting the Root Cause Analysis,

and Responding with Appropriate Corrective and Preventive Actions

4th Clinical Quality Signals, RCA and CAPA

EXECUTIVE SUMMARY

CONTENTS

INTRODUCTION: THE 4TH CLINICAL QUALITY SIGNALS, RCA AND CAPA CONFERENCE 3

2014 SESSION SUMMARIES 4

RESOURCES FOR INFORMATION AND DISCUSSION 11

3www.exlevents.com/CAPA

INTRODUCTION: THE 4TH CLINICAL QUALITY SIGNALS, RCA AND CAPA CONFERENCE

If you weren’t able to join us this year, here is what you missed at the

4th Clinical Quality Signals, RCA and CAPA Conference …

With the theme of “Identifying Clinical Non-compliance, Conducting the Root Cause

Analysis, and Responding with Appropriate Corrective and Preventive Actions,” the

4th annual summit, held January 28-29 in Alexandria, Virginia, served as a gathering

for clinical quality and operations professionals from companies of all sizes and

types to discuss and share their experiences. This event continues to act as the

only industry forum dedicated to identifying non-compliance, understanding the

root cause and executing corrective and preventive actions in the GCP environment,

and provides a unique forum for candidly sharing experiences, best practices and

lessons learned.

This summit brought together professionals from pharmaceutical, biotechnology

and medical device companies as well as CROs and other clinical trial service

providers, who work in quality systems development, management and training,

clinical quality assurance and control, clinical operations and management, GCP

compliance, clinical auditing, monitoring, and more.

Through the use of an audience response system, speakers were able to poll

the audience, which provided valuable insight into the industry’s perceptions,

understanding and progress as they related to the topics discussed. These topics

included effective tools for identifying clinical non-compliance and assessing the

criticality, prioritizing and managing findings to determine the response, conducting

an effective root cause analysis, initiating a CAPA process and developing a system,

employing proactive approaches to prevent non-compliance and much more,

including the critical site perspective and the role of clinical monitoring.

Following are session summaries and highlights to give you an idea of the

information presented and topics discussed at the 4th Annual Clinical Quality

Signals, RCA and CAPA Conference.

2014 Audience Breakdown

- Pharmaceutical, Biotech, Medical Device Companies

- CROs

- Other Clinical Service and Technology Providers

- Sites

65%

10%20%

Company Type

5%- Quality/Compliance

- Clinical Operations/Management

- Audits/Inspections

- Other

60%

10%

20%10%

Department

http://exlevents.com/5th-clinical-quality-signals-rca-capa/


In the Chairperson’s opening remarks, Kevin Wilson,

the Manager of Global Medical Quality Systems for

Eli Lilly, talked about building a common language,

and behaviors for success, such as creating a culture

of accountability rather than a culture of blame.

He surveyed the audience on what signals they

are currently tracking and 70% indicated audit

observations, deviations and non-compliance.

With regards to root cause, 58% said they are

conducting root caused based on levels of

criticality with 43% indicating Quality teams have

responsibility for documenting the root cause.

In the opening session, Celeste Gonzalez, Senior

Clinical Quality Assurance Specialist at Boston

Scientific, discussed “Strategies for Identifying

Clinical Non-Compliance and Assessing the

Criticality at the Sponsor, CRO and Site Levels.”

After defining the importance of clinical quality

signals, she outlined different sources to use for

identification and shared examples of clinical QA

audit findings, providing guidance for uncovering,

categorizing and analyzing these signals, including

determination of the severity, scope and impact.

A panel discussion on management and

prioritization focused on “Practical Tools and

Methodologies for Prioritizing and Managing

Findings to Determine an Adequate Response.”

The panel was moderated by Lynn Van Dermark,

CEO of Medtrials, Inc. and the panelists included:

Suzanne Elliott, Associate Director, R&D Compliance

& Process, Continuous Quality Improvement at

Shire; Venessa Galate, Director Quality Process

Liaison, Janssen Pharmaceuticals; and Sunil

Kotecha, Corporate Audit for Pfizer. The group

discussed tools and methodologies for categorizing

and prioritizing non-compliances, the departments

responsible for managing non-compliance and the

levels of visibility.

During the panel, the audience was asked to

consider the following scenario: “Gaps were

identified in the timely distribution of SUSAR to

the investigator sites. Who should be involved in

determining appropriate actions?” The response

was split with about a third selecting Safety/PV

Group, another third selecting Study Management

4th Clinical Quality Signals, RCA and CAPA – January 28-29, 2014 www.exlpharma.com/clinicalCAPA

What signals are you tracking?

1 2 3 4

15%

70%

9%7%

1.  Audit Observations 2.  Deviations 3.  Non-compliance 4.  All of the above


Conduct root cause based on?

1 2 3 4

58%

9%9%

23%

1.  Levels (Critical, Major, Other)

2.  Risk analysis 3.  All signals get a

CAPA 4.  Management

review


Who documents the root cause?

1 2 3 4 5 6

23%

43%

11%

0%

11%11%

1.  Clinical Operations 2.  Quality 3.  Compliance 4.  Audited area 5.  General admin 6.  Other

SESSION SUMMARIES

3 Boston Scientific Confidential -- For Internal Use Only. Do Not Copy, Display or Distribute Externally

Importance of Clinical Quality Signals ACHIEVE and MAINTAIN

•  Data Integrity •  Subject Protection •  Subject Safety •  Protocol Compliance •  SOP Compliance •  Compliance with national/regional/local

regulations and requirements •  Compliance with various contractual

agreements Sponsor CRO Investigative sites IRB

Clinical Quality Signals, RCA & CAPA, January 28-29, 2014, Alexandria, VA



Staff/CRA and 39% indicating Another Combination

of Staff.

And when polled about the following: “During a

routine audit, several protocol deviations were

identified at an investigator site. Who should be

involved in determining appropriate actions?” 57%

responded with Study Management Staff/CRA.

On the topic of Responding to Non-Compliance,

Jeanette Johnson, Manager of Consulting Services

at Pathwise, offered a presentation on “Developing

the Necessary and Appropriate Actions for

Different Types of Audit Findings.” She noted

the importance of characterizing findings and of

gathering specifics. Each problem statement should

answer: What is the problem? What requirement

was met? What evidence is there to show that the

requirement was not met? Jeanette provided

valuable insight on defining actions, based on the

criticality of the finding. In her polling, 76% of

companies were reported to have escalation criteria,

but only 16% had de-escalation criteria.

She went on to discuss effective risk evaluation

indicating it should include two separate actions,

assessing the impact and frequency, and deciding

where the event will be recorded in the quality

system. Then she addressed using that evaluation

for risk-based decision-making to implement

actions, noting that decisions within the CAPA

system should be based on risk commensurate

to complexity, risk-based decisions should occur

throughout the CAPA process to meet regulatory

expectations, and it’s necessary to document the

rationale for the actions throughout the CAPA

process. Concluding with, the most successfully

implemented CAPAs are managed by operational

teams, have management buy-in, and are shared

throughout the organization.


Gaps were identified in the timely distribution of SUSAR to the investigator sites.

Who should be involved in determining appropriate actions?

1 2 3 4

31%

39%

31%

0%

1.  Safety/PV Group 2.  Study Clinician/ Legal 3.  Study Management

Staff/ CRA 4.  Another Combination

of Staff


During a routine audit, several protocol deviations were identified at an investigator site.

Who should be involved in determining appropriate actions?

1 2 3 4

5%

38%

57%

0%

1.  Audit Department 2.  Study Clinician/ Legal 3.  Study Management

Staff/ CRA 4.  Another Combination

of Staff



A panel discussion on “The Role of Clinical

Monitoring: Developing and Training Clinical

Monitors to Identify Non-Compliances Early,

Quickly and Efficiently to Facilitate Necessary

Escalation” was moderated by Liz Wool, President

and CEO of QD-Quality and Training Solutions,

Inc. Panelists were: Dwayne Brazelton, Director of

Clinical Quality Assurance for Macrogenics, Inc.;

Celeste Gonzalez, Senior Clinical Quality Assurance

Specialist for Boston Scientific; Jennifer LaLonde,

Director of Research for the Cardiac and Vascular

Research Center of Northern Michigan; and Sue

Latham, Senior Manager of Quality Assurance for

Medtrials, Inc. The discussion included strategies

for CRA training, approaches to confirming

competency, identifying and overcoming common

challenges and what has been deemed “critical” for

CRA performance.

When polled, just over half of the audience said

their companies had a training program for issue

identification and management and half also

indicated they had a training program for root cause

analysis and CAPA methods.

When asked about the effectiveness of such

programs, no one in the group said that their

company’s training programs were extremely

effective and 39% indicated they were just average.

When asked if a process is established for the sites

to give feedback to the sponsor regarding the

clinical monitor, only 10% of the audience answered

yes, with 55% indicating no and 35% not knowing.

Day two led off with a panel discussion on

“Effective Root Cause Analysis” offering the

perspectives of experts who shared their company’s

processes, best practices and lessons learned when

conducting root cause analyses. The moderator

was Diane Carter, Clinical Quality Auditor for BTG,

and panelists were: Venessa Galate, Director Quality

Process Liaison, Janssen Pharmaceuticals; Helen

Labus, Compliance Director, Global R&D Quality,

Amgen; and Jamie Sweeney, Director of Quality

Management, Research Pharmaceutical Services.


Question #1 Do you have a training program for

issue identification and management?

1 2

48%

53%1.  Yes 2.  No


Question #2 Do you have a training program for

root cause analysis and CAPA methods?

1 2

50%50%

1.  Yes 2.  No


Question #3 How effective is your training program?

1 2 3 4 5

0%

27%

0%

33%

39%1.  Extremely effective 2.  Very effective, but

there’s always some room for improvement

3.  Average 4.  Not very effective, needs

much improvement 5.  Terrible, not effective at

all


Question #4 Do you have a process established for sites to give

feedback to the Sponsor regarding the Clinical Monitor?

1 2 3

10%

35%

55%1.  Yes 2.  No 3.  I don’t know



Audience polling revealed that more than half

have an immature CAPA process, and that only

one-third of companies have a formal process for

communicating RCA results to the organization and

partners.

The panel offered a brief overview of the tools and

philosophies they use when conducting an RCA,

who leads the investigation at their companies,

tips for managing costs when conducting an RCA,

communication strategies and what to do when

the sponsor and CRO differ on their assignment of

cause.

“Utilizing the Results from the Root Cause Analysis

to Develop Effective and Corrective Preventive

Actions” was presented by Brett Preston and

Kristine Yahagi, both of the Quality Process Liaison

group at Janssen Pharmaceuticals. They shared the

key elements of an executed root cause analysis,

and discussed the importance of writing a SMART

(specific, measurable, achievable, relevant and time-

bound) CAPA.

Establishing the link between RCA and CAPA, they

noted since CAPA seeks to eliminate root causes,

corrective/preventative actions should directly

correlate to one or more of the identified root

causes and when working with multiple causes, it’s

important to prioritize based on risk. Validating

the CAPA includes expert weigh-in, roundtable

discussion and validity confirmation (or not) via

effectiveness checks. The presenters also provided

insight on how to document and record the CAPA

and what information should be captured.

Jennifer LaLonde, Director of Research at the

Cardiac and Vascular Research Center of Northern

Michigan provided the critical site perspective with

a presentation on “Understanding Compliance

Obstacles at the Site Level and How Sponsors

Can Best Support sites to Optimize Quality.” She

discussed the common obstacles to compliance

at the sites that included comprehension/

interpretation of protocol, complex and/or


How mature is your company/organization’s CAPA process

1 2 3

51%

20%

29%

1.  Immature/newly developed

2.  Fairly established with moderate experience

3.  Mature process with multiple iterations of development


Does your company/organization have a formal process for communicating the RCA results to the organization

and partners?

1 2 3

33%

7%

60%1.  Yes 2.  No 3.  Don’t Know

Elements of an Executed Root Cause Analysis

Summary of event or nonconformance

Sequence of events (including dates and Jmes where applicable)

List of implicated products or processes

Summary of immediate correcJons that have been completed

Summary of root cause invesJgaJon

9 ExL Pharma 4th Clinical Quality Signals, RCA and CAPAs Conference January 29, 2014

30

Documenting RCA and CAPAs: Depth of Information

• Summary of event or nonconformance • Sequence of events • List of implicated products or processes • Summary of immediate completed correcJons • Summary of root cause invesJgaJon

RCA • AcJon Type (CA vs PA) • AcJon DescripJon • Due Date • Owner • Department • GCP and/or PV and/or GLP • Pharma and/or Consumer and/or Medical Devices

CAPA

ExL Pharma 4th Clinical Quality Signals, RCA and CAPAs Conference January 29, 2014



difficult to understand inclusion and exclusion

criteria, unclear or unknown communication plan

when the sites need to make contact with the

trail sponsor, and lack of expertise with study

provided equipment. To improve compliance, she

recommended sponsors differentiate their training

based on the experience level of the coordinators,

bringing the “new-bies” in early to learn

fundamentals and basics. She also accentuated the

importance of communication, and establishing an

open relationship where the sites want to call and

share their discovery at the first occurrence.

When asking the audience about their policy for

remote monitoring, 55% of the audience indicated

they do not have remote monitoring. Sharing the

impact of risk-based monitoring at the site level,

Jennifer indicated it as a loss of reassurance with a

sense that there are no more checks and balances.

She recommended query resolutions as the best

tool for determining if the site is on track when

executing risk-based monitoring. She concluded by

stating that research is a team effort and you must

lay down a strong foundation and give your sites

“longevity.”

“Deconstructing a Broken Clinical Trial; Rebuilding

with CAPA-Driven Processes to Successfully

Rescue the Trial” was a case study shared by

Nancy Showden, CEO of NCGS, Inc. She described

a critical path compound trial that was near

termination and how to determine when a rescue is

necessary. She then outlined how to deconstruct

and reconstruct the trial using RCA, CAPA and

quality by design. This included executing a

comprehensive assessment of failed processes,

rapid rescue implementation, understanding the

elements and related impact, identifying the root

cause(s), mapping the CAPA scope, understanding

the risk (current, future and enterprise), developing

a plan with stakeholder support, measuring the

success of interventions and reconstruction, and

sustainability.

Krista Kerr, Associate Director, Team Lead

Global R&D Quality & Compliance at Janssen

Pharmaceuticals offered a session on “Employing

Proactive Approaches for Determining Potential

Problem Areas to Prevent Non-compliance and

CAPA.” She noted challenges to quality and

compliance, including increasing complexity

and globalization, evolving regulations and

requirements, emerging regulators and regulations,

an even greater number of third parties, and rapid

evolution and adoption of new technologies.

She accentuated that proactive compliance

includes strategies to proactively manage the

risk to organizations and prevent or reduce the

likelihood of non-compliance; to that end, quality

should be integrated into day-to-day processes and

companies should continually monitor processes

and service providers and collect/analyze data to

identify trends, determine root causes and enact

process improvement. She reminded the audience

that the goal is to identify issues before they occur,

and that the benefits of proactive compliance

include increased likelihood of achieving objectives,

performance improvements, informed choices and

Question Do you have a policy for Remote Monitoring?

1 2 3 4

6%

55%

18%21%

1.  Mandated by occurrence 2.  Mandated by the

calendar 3.  Mandated by Subject

Enrollment/Follow-‐up 4.  Do not have remote

monitoring



decisions, efficiency, consistent and reliable results,

and the facilitation of continual improvement.

Next was a case study presentation by Elizabeth

Luczak, Vice President, Medical Regulatory

Compliance at Pfizer detailing the “Development

and Implementation of a Global CAPA Process

to Optimize Reporting and Gain Insight into

Process Gaps and Potential Non-Compliance.”

When polling the audience, she found that 37% are

working with site and function based CAPA systems

that are NOT global, and that the biggest challenges

in implementing/maintaining the current CAPA

system were sponsorship from senior management

and engagement of critical team members.

She noted key factors to the success/failure of

sustained CAPA outcomes include ownership/

engagement, accountability/empowerment,

investigation, formality of implementation,

communication/training, outcomes demonstrated,

monitoring sustained effectiveness and changes

post-CAPA closure. She shared valuable

insight from her experiences on the key goals/

considerations for a global CAPA system, including

• Escalation/line of sight to significant

quality issues

• Global standards across medical

processes/interconnectedness

• Proactive identification of significant

quality issues

• Engagement/ownership

• Quality of the investigation to determine

scope of impact and scope

of CAPA required

• Preventing future/repeating quality issues

• Visibility/transparency of execution status

and risk

• Quality improvement

• Integration in quality management system

19

Proactive Compliance Consistent and considered approach to risk management

Qualita3ve, metric-‐based risk assessment process

Awareness of interdependent risks

Ongoing monitoring for awareness of changing risk profiles

Integra3on of quality into processes and opera3ons

Culture of con3nuous improvement

Proac3vely apply informa3on across the enterprise

Question How global is your current CAPA system?

3

1 2 3 4 5 6

37%

18%

3%

13%

21%

8%

1.  Not global – site and function based

2.  Global across GCP/Clinical Trial Execution

3.  Global across GCP and Pharmacovigilance (PV)

4.  Global across GCP/PV and Other Medical Areas

5.  Enterprise Global 6.  Other

Question What is your biggest challenge in implementing/maintaining your CAPA system?

9

1 2 3 4 5 6

30% 30%

3%

8%

20%

10%

1.  Sponsorship from Sr. Management

2.  Engagement of critical team members

3.  Quality of investigation 4.  Prioritizing CAPA

execution 5.  Tools and systems 6.  Other



The concluding panel discussion on System

Implementation shared “Best Practices and Lessons

Learned for Defining and Implementing a System for

Tracking, Escalating and Correcting Non-Compliances

and Preventing Reoccurrence.” The panel moderator

was Kevin Wilson, Manager, Global Medical Quality

Systems, Eli Lilly; panelists were Pearl Boakye,

Head of Compliance Management, Bayer; Paula

Parsons, Compliance Senior Manager, Amgen; Jamie

Sweeney Director of Quality Management, Research

Pharmaceutical Services.

When determining what is meant by the word

“system,” ninety-six percent of audience members

defined a CAPA system as a process and practice for

recording and tracking CAPA, which may or may not

include an electronic tool, while only four percent

defined it as a computer system or electronic tool for

recording and tracking CAPA.

The panelists shared tips for designing a cost-effective

system that meets required needs, strategies for

obtaining corporate buy-in and resources to develop

and implement a clinical CAPA system, best practices

for informing, educating and training internal teams

on the importance of CAPA and the CAPA system,

determining clinical partners accessibility and visibility

of the CAPA system and common obstacles to

development and implementation and the steps that

were taken to overcome them.



RESOURCES FOR INFORMATION AND DISCUSSION

5TH SIGNAL DETECTION, ROOT CAUSE ANALYSIS AND CAPA SUMMIT

The 5th Signal Detection, Root Cause Analysis and CAPA summit taking place

January 22-23, 2015, will address the main considerations for implementing a pre-

market CAPA system that ensures quality in clinical operations and addresses post-

market CAPAs that touch upon risk assessment and post-market surveillance in

order to support product safety and compliance. This unique event is designed to

help all life science organizations gain insights on how to develop corrective action

plans and tremendously improve proactive preventive plans.

Please visit www.exlevents.com/CAPA to learn more!

PROACTIVE GCP COMPLIANCE ONLINE DISCUSSION GROUP

Discuss the topics addressed during this conference as well as other GCP-related

subjects by becoming a member of the Proactive GCP Compliance LinkedIn®

Discussion Group. With close to 2000 members, this active group offers a valuable

forum for learning from and engaging with like-minded professionals all focused on

optimizing clinical quality management and improving clinical performance. Use

this forum to ask questions, share best practices, link to relevant articles and white

papers and learn from one another. Click here and request to join.

http://www.linkedin.com/groups/Proactive-GCP-Compliance-2914634/about



Documents

EXECUTIVE SUMMARY 4th Clinical Quality Signals, RCA and CAPAinfo.exlevents.com/rs/exlevents/images/C405-Executive... · 2014-10-20 · 3 INTRODUCTION: THE 4TH CLINICAL QUALITY SIGNALS,